title: Soluble polymer supported divergent synthesis of tetracyclic benzene-fused pyrazino/diazepino indoles: an advanced synthetic approach to bioactive scaffolds.
abstract: The synthesis of indoline substituted nitrobenzene on a PEG support and its further elaboration to structurally diverse benzene-fused pyrazino/diazepino indoles is disclosed. A reagent based diversification approach coupled with Pictet-Spengler type condensation reactions furnished these fused polycyclic scaffolds. Microwave irradiation was used as a means of rate acceleration for soluble polymer-supported reactions. The efficiency of these fused heterocyclic molecules to inhibit the vascular endothelial growth factor receptor 3 (VEGFR-3) was examined in vitro using kinase receptor activation enzyme-linked immunosorbant assay (KIRA-ELISA). Based on the preliminary results obtained, a small set of potential drug candidates were identified as novel leads in this therapeutic area to be further explored as anti-metastatic agents.
authors.affiliation: Laboratory of Combinatorial Drug Discovery, Department of Applied Chemistry National Chiao Tung University, Hsinchu 300-10, Taiwan.
authors.forename: Po-Tsung
authors.initials: PT
authors.lastname: Lin
authors.forename: Deepak B
authors.initials: DB
authors.lastname: Salunke
authors.forename: Li-Hsun
authors.initials: LH
authors.lastname: Chen
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Sun
mesh_terms: D001381:Azepines / Q000737:chemistry*; D001554:Benzene / Q000138:chemical synthesis* / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011719:Pyrazines / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors
chemical_list: D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011092:Polyethylene Glycols; D040321:Vascular Endothelial Growth Factor Receptor-3; D001554:Benzene